This proposal aims to understand the changes in visual processing that occur when subjects shift between alert and non-alert waking states. Thanks to the development of behavioral methods for the control of eye position, great advances have been made in understanding central mechanisms of visual perception of alert, attentive subjects. However, there is little understanding of cortical processes that come into play when alertness wanes. The awake, non-alert state is not equivalent to anesthesia, or to sleep states. When non-alert, we are capable of perception, but our perceptual capacities differ. It is commonly believed that accidents happen when we are not alert, but the extent to which early thalamic or visual cortical mechanisms may be responsible for this (as opposed to higher cognitive processes) is an open question. This proposal relies on a unique model system that is very well-suited to address this question: the awake rabbit, an animal whose inner mental life transparently shifts between alert and non- alert states, and whose stable eyes and diffident nature make it an ideal subject for these experiments. The proposed research will examine how changes in the brain state of awake subjects influence the multiple, sequential stages of information processing that occur within the visual thalamocortical and intracortical network. The experiments will measure state- dependent changes in the visual response properties of excitatory and inhibitory neurons at the input and output layers of the cortex and will investigate the underlying mechanisms leading to these changes, at the subthreshold and spiking level. This work will lead to a better understanding of cortical mechanisms of visual processing in a dynamic, awake brain. From a health perspective, these studies will have an important impact on our understanding of how alertness/vigilance deficits can impact visual perception and performance, and will provide the basis for future clinical studies of human mental health and behavioral disorders. PUBLIC HEALTH RELEVANCE: The current work will have an important impact on our understanding of how alertness/vigilance deficits can impact visual perception and performance. A disruption in response gain within thalamocortical systems has been associated with mental diseases that involve changes in sensory processing and the level of vigilance. This proposal will reveal the mechanisms that modulate response gain within the visual thalamocortical system and, by doing so, it will provide the basis for future clinical studies of human mental health and behavioral disorders.